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New Treatments for Infertility

Amongst the factors in women that one has to seriously consider are ovulatory dysfunction, the most common problem that we face, along with tubal disease. This varies in studies from forty to fifty percent, depending on who you read, but it is a large number of infertility.

Why is this such a big problem now? It is even more of a problem now than it was years ago because of the aging demographics of the female population in the United States. Without a doubt, the number one type of patient that we see and probably most reproductive endocrinologists and general gynecologists see is the patient who has a career, who has delayed having children until the mid to late 30's and is now faced with this dilemma.

If you look at the numbers from the Census Bureau, clearly the number of women who are older have increased and will increase as time goes on, by the middle of this century. The number one thing that we can absolutely document is that fecundity - the ability to conceive.

We are beginning to try to talk about the perimenopausal period. Probably the best way to assess this is a day three FSH. On day three of the cycle, it may take 5 miu/ml to get a certain level of estrogen when you are 20 years old. To get that same level of estrogen when you are 40 years old might take 10 to 15 miu/ml of FSH. While phenotypically the person may still be ovulatory and may have no difference in anything other than this biochemical change, it clearly represents incipient ovarian failure as a woman ages. The other more recent test that people are doing is inhibin.

Inhibin is a peptide that comes from the ovary. As the ovary fails, the level of inhibin B drops. So you are looking for low inhibin B and FSH when you are trying to document incipient ovarian failure. Clearly, phenotypically the length of the follicular phase is what changes; once the person ovulates, the length of the luteal phase is pretty sacrosanct at 14 days in humans.

A study came out of California that was updated about five years ago. Patients were categorized based on age; less than 30, 30 to 34, 35 to 39, greater than 40, and day three FSH's were measured on everybody. They also measured all sorts of other parameters; how high did their estradiol get; how many eggs did they get; how many of those eggs were fertilized; how many of those people had implantation and pregnancy resulting from their IVF.

With IVF, independent of any other variable, just age, ongoing pregnancies per embryos transferred, about fifty percent at less than 30 linearly drops down to almost nothing by the time a person is over 40; there are just a handful of pregnancies.

What is a semen analysis? The numbers you need to remember are 20 million motile sperm per cc in the ejaculate and 3 to 5 ml is the normal ejaculate and at least fifty percent normal forms - normal morphology. The reason that the numbers are low - fifty percent.

Pretty much the one male factor that everyone talks about is varicocele. It is really quite controversial. Does it even cause infertility? Does it cause oligospermia? Does it cause azoospermia? The truth is that we don't actually know the answer to that question. We also clearly don't know the answer as to whether or not varicocelectomy - removing it - makes a bit of difference. I can tell you that there is no randomized trial to answer that question and you can find just as many cohort studies of people who stay that removing it will make a difference as people who say that removing it doesn't, regardless of their background.

There are a lot of other reasons for male factor infertility and they pretty much follow all of the things of female ovulatory disorders. They are hypogonadotropic and hypergonadotropic. If you have low gonadotropins - usually we are talking about FSH - then you think of things that are more central. Anything from hyperprolactinemia, hypothyroidism, all the same things you think about in a woman. If they are hypergonadotropic, then you have to think of testicular failure.

When I was a resident, we did post coital tests on absolutely everybody; even when I was a Fellow, we did it on almost everybody. The truth is, however, that it doesn't make a lot of sense. The definition of a normal post coital is at least 10 to 20 normal motile sperm in the little swab that you take from the cervix, usually four to five hours after intercourse, without any white cells

How do you treat male factor? Primarily, you try to concentrate the number of sperm that you do have and then give it to her in an intrauterine insemination. Why not just put it in the vaginal intracervically? This question was answered recently in a New England Journal of Medicine article from about two years ago. There was a multicenter national trial in which they showed that in people who had ovulation induction, if you gave them intrauterine insemination (IUI) they had a three-fold better chance of getting pregnant with a confidence interval of 2.5 to 3.0. That

The more high-tech way of dealing with male infertility now is intracytoplasmic sperm injection (ICSI). The setup that we actually have boils down to a way of taking a single sperm and injecting it into an egg that is aspirated after ovulation induction. That sperm, interestingly, can be obtained from the ejaculate the old fashioned way, or it can be obtained from a needle in the vas, or it can be obtained from testicular biopsy, which means that you are taking an immature, immotile sperm and we can now mature those sperm in vitro to the point where they are motile,

The second big area that we need to talk about is ovulation. Ovulatory defects in women make up about forty percent of their cause of infertility. The classic example is polycystic ovarian disease. You need to come to a diagnosis as to what is causing them to be an- or oligoovulatory. There are a lot of other reasons for anovulation, including hyperprolactinemia as a cause, any sort of stress and issues around nutrition that will make a patient oligo- or anovulatory,

What are some of the types of ovarian dysfunction? Hypothalamic, hyperprolactinemia, hyperthyroidism, hypothyroidism, premature ovarian failure. The workup is essentially the same workup for secondary amenorrhea. All you have to remember, besides measuring beta hCG,

There is a very interesting study from Canada in which they randomized people going for laparoscopy for whatever purpose - usually pain - and who wanted to get pregnant, to either get treatment or just have a diagnostic laparoscopy and then pull out, unless they saw something very severe. If they had minimal or mild endometriosis, and those people who were randomized to treatment - had a significantly higher rate of pregnancy beyond 20 weeks than the group that

Finally, a review of fibroids and all sorts of uterine defects. Clearly, if you have a fibroid that invades the tube and blocks it, that is a problem. If you have a submucous fibroid that impedes implantation, that is also a big problem. You can have all sorts of different kinds of fibroids and